DESCRIPTION: (Principal Investigator's) A detailed study of CC-1065 and the duocarmycins, exceptionally potent antitumor antibiotics, are described. CC-1065 and the duocarmycins derive their biological properties through a sequence selective alkylation of duplex DNA which proceeds by reversible, stereoelectronically-controlled adenine N3 addition to the least substituted carbon of the activated cyclopropane within minor groove 5 or 3.5 base pair AT-rich sites, respectively. Further studies to define the characteristics of the alkylation reaction, to determine the origin of the DNA alkylation selectivity and the source of catalysis, and to define fundamental principles underlying the relationships between structure, chemical or functional reactivity, DNA alkylation properties, and biological activity are detailed.